Is STRC p.Arg92Pro (c.275G>C) pathogenic?

STRC p.Arg92Pro (c.275G>C) is classified Uncertain significance in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-10). AlphaMissense: ambiguous (0.4222); Very rare (popmax 0.00261%, eas); Associated with Inborn genetic diseases.

What condition is associated with STRC p.Arg92Pro (c.275G>C)?

STRC p.Arg92Pro (c.275G>C) is associated with Inborn genetic diseases (ClinVar).

How common is STRC p.Arg92Pro (c.275G>C) in the general population?

STRC p.Arg92Pro (c.275G>C) is very rare (popmax 0.00261%, eas) (gnomAD).

What do computational predictors say about STRC p.Arg92Pro (c.275G>C)?

AlphaMissense predicts ambiguous (score 0.4222) — an in-silico prediction, not a clinical call.

STRC p.Arg92Pro

c.275G>C · VCV3450855

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4222 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00261%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4222	ambiguous
REVEL	0.597	indeterminate
SaProt	LLR -5.92	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP -0.41, phastCons 0.71
Regional constraint	o/e 0.00	constrained · MANE · 7,566 bp · p 1.3e-74 · regional, not allelic
Overall
CADD	19.86	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00261% East Asian · 1/38,256 alleles

Overall 8.85e-05% 1/1,130,150 alleles · very rare exomes 1/993,736 · genomes 0/136,414 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: STRC
Protein: p.Arg92Pro
Coding: c.275G>C
MANE Select: NM_153700
Type: single nucleotide variant
Location: chr15:43618146 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.21

Full STRC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STRC p.Arg92Gln Uncertain significance ★★ ⚠ same residue
STRC p.Arg92Trp Uncertain significance ★★ ⚠ same residue
STRC c.4701+1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1102Gln Uncertain significance ★★ ⚠ same condition
STRC p.Arg1237Trp Uncertain significance ★★ ⚠ same condition
STRC p.Arg1338Gln Uncertain significance ★★ ⚠ same condition
STRC p.Arg56His Uncertain significance ★★ ⚠ same condition
STRC p.Arg832Trp Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/strc-p-arg92pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown